scholarly journals Povidone Iodine: Properties, Mechanisms of Action, and Role in Infection Control and Staphylococcus aureus Decolonization

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Didier Lepelletier ◽  
Jean Yves Maillard ◽  
Bruno Pozzetto ◽  
Anne Simon
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Resistance ◽  
Povidone Iodine ◽  
Ex Vivo ◽  
Cross Resistance ◽  
Content Type ◽  
Intranasal Mupirocin ◽  
Resistant Strains ◽  
Emergence Of Resistance

ABSTRACT Nasal decolonization is an integral part of the strategies used to control and prevent the spread of methicillin-resistant Staphylococcus aureus (MRSA) infections. The two most commonly used agents for decolonization are intranasal mupirocin 2% ointment and chlorhexidine wash, but the increasing emergence of resistance and treatment failure has underscored the need for alternative therapies. This article discusses povidone iodine (PVP-I) as an alternative decolonization agent and is based on literature reviewed during an expert’s workshop on resistance and MRSA decolonization. Compared to chlorhexidine and mupirocin, respectively, PVP-I 10 and 7.5% solutions demonstrated rapid and superior bactericidal activity against MRSA in in vitro and ex vivo studies. Notably, PVP-I 10 and 5% solutions were also active against both chlorhexidine-resistant and mupirocin-resistant strains, respectively. Unlike chlorhexidine and mupirocin, available reports have not observed a link between PVP-I and the induction of bacterial resistance or cross-resistance to antiseptics and antibiotics. These preclinical findings also translate into clinical decolonization, where intranasal PVP-I significantly improved the efficacy of chlorhexidine wash and was as effective as mupirocin in reducing surgical site infection in orthopedic surgery. Overall, these qualities of PVP-I make it a useful alternative decolonizing agent for the prevention of S. aureus infections, but additional experimental and clinical data are required to further evaluate the use of PVP-I in this setting.

scholarly journals Impact of Exposure of Methicillin-Resistant Staphylococcus aureus to Polyhexanide In Vitro and In Vivo

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
A. Renzoni ◽  
E. Von Dach ◽  
C. Landelle ◽  
S. M. Diene ◽  
C. Manzano ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Resistance ◽  
Broth Culture ◽  
Cross Resistance ◽  
Methicillin Resistant ◽  
Content Type ◽  
Genomic Changes ◽  
Low Concentrations

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increases the need for development of alternative decolonization molecules. The absence of reported severe adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as a topical antiseptic. In the present study, we evaluated the in vitro and in vivo capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the in vitro emergence of reduced susceptibility to polyhexanide by prolonged stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the mprF and purR genes and with concomitant decreased susceptibility to daptomycin and other cell wall-active antibiotics. However, the in vitro emergence of reduced susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine. During in vivo polyhexanide clinical decolonization treatment, neither reduced polyhexanide susceptibility nor chlorhexidine cross-resistance was observed. Together, these observations suggest that polyhexanide could be used safely for decolonization of carriers of chlorhexidine-resistant S. aureus strains; they also highlight the need for careful use of polyhexanide at low antiseptic concentrations.

scholarly journals Lead Optimization of Dehydroemetine for Repositioned Use in Malaria

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Priyanka Panwar ◽  
Kepa K. Burusco ◽  
Muna Abubaker ◽  
Holly Matthews ◽  
Andrey Gutnov ◽  
...  
Keyword(s):  
De Novo ◽  
Antimalarial Activity ◽  
Drug Repositioning ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Synthetic Analogue ◽  
80S Ribosome ◽  
Content Type ◽  
Resistant Strains

ABSTRACT Drug repositioning offers an effective alternative to de novo drug design to tackle the urgent need for novel antimalarial treatments. The antiamoebic compound emetine dihydrochloride has been identified as a potent in vitro inhibitor of the multidrug-resistant strain K1 of Plasmodium falciparum (50% inhibitory concentration [IC50], 47 nM ± 2.1 nM [mean ± standard deviation]). Dehydroemetine, a synthetic analogue of emetine dihydrochloride, has been reported to have less-cardiotoxic effects than emetine. The structures of two diastereomers of dehydroemetine were modeled on the published emetine binding site on the cryo-electron microscopy (cryo-EM) structure with PDB code 3J7A (P. falciparum 80S ribosome in complex with emetine), and it was found that (−)-R,S-dehydroemetine mimicked the bound pose of emetine more closely than did (−)-S,S-dehydroisoemetine. (−)-R,S-dehydroemetine (IC50 71.03 ± 6.1 nM) was also found to be highly potent against the multidrug-resistant K1 strain of P. falciparum compared with (−)-S,S-dehydroisoemetine (IC50, 2.07 ± 0.26 μM), which loses its potency due to the change of configuration at C-1′. In addition to its effect on the asexual erythrocytic stages of P. falciparum, the compound exhibited gametocidal properties with no cross-resistance against any of the multidrug-resistant strains tested. Drug interaction studies showed (−)-R,S-dehydroemetine to have synergistic antimalarial activity with atovaquone and proguanil. Emetine dihydrochloride and (−)-R,S-dehydroemetine failed to show any inhibition of the hERG potassium channel and displayed activity affecting the mitochondrial membrane potential, indicating a possible multimodal mechanism of action.

scholarly journals 569. Evaluation of a Povidone-Iodine Preparation for Nasal Decolonization of Methicillin-Resistant Staphylococcus aureus

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S269-S269
Author(s):  
Hussein Abou Ghaddara ◽  
Jennifer Cadnum ◽  
Y Karen Ng Wong ◽  
Curtis Donskey
Keyword(s):  
Staphylococcus Aureus ◽  
Povidone Iodine ◽  
Perioperative Period ◽  
Control Group ◽  
Single Application ◽  
Methicillin Resistant ◽  
Dosing Intervals ◽  
And Control ◽  
Emergence Of Resistance

Abstract Background Mupirocin is commonly used for nasal decolonization of Staphylococcus aureus, but it has limitations including frequent emergence of resistance and non-adherence due to the need for repeated applications. Povidone-iodine is increasingly used as an alternative for nasal decolonization because it has a low propensity for emergence of resistance and rapid in vitro antibacterial activity. However, limited data are available on the microbiological efficacy of povidone-iodine for suppression of nasal S. aureus. Methods We compared the effectiveness of a single application or 5 days of twice daily application of a commercial 10% povidone-iodine preparation vs. phosphate-buffered saline for a reduction in nasal MRSA in methicillin-resistant S. aureus (MRSA)-colonized patients (9–11 per treatment group). Nasal swabs were collected for quantitative culture of MRSA before and at 1, 6, 12 and 24 hours after the single application or before each dose for the 5-day regimen. Analysis of variance was used to compare MRSA colony counts in povidone iodine vs. control patients. Results The concentrations of MRSA in the nares were similar for povidone-iodine and control group patients prior to treatment. As shown in the figure, the single application of povidone-iodine resulted in a statically significant reduction in nasal MRSA in comparison to controls at 2 and 6 hours after treatment (P10 colonies per swab). Conclusion Our findings suggest that single preoperative applications povidone-iodine could be useful for short-term suppression of S. aureus during the perioperative period. Additional studies are needed to evaluate the efficacy of the povidone-iodine preparation for MRSA decolonization when used at more frequent dosing intervals or in combination with chlorhexidine bathing. Disclosures All authors: No reported disclosures.

scholarly journals Missense Mutations in PBP2A Affecting Ceftaroline Susceptibility Detected in Epidemic Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Clonotypes ST228 and ST247 in Western Switzerland Archived since 1998

2015 ◽  
Vol 59 (4) ◽  
pp. 1922-1930 ◽  
Author(s):  
William L. Kelley ◽  
Ambre Jousselin ◽  
Christine Barras ◽  
Emmanuelle Lelong ◽  
Adriana Renzoni
Keyword(s):  
Staphylococcus Aureus ◽  
University Hospital ◽  
Surveillance Program ◽  
Missense Mutations ◽  
Unknown Parameters ◽  
Methicillin Resistant ◽  
Content Type ◽  
Resistant Strains ◽  
Mrsa Strains

ABSTRACTThe development and maintenance of an arsenal of antibiotics is a major health care challenge. Ceftaroline is a new cephalosporin with activity against methicillin-resistantStaphylococcus aureus(MRSA); however, no reports concerning MRSA ceftaroline susceptibility have been reported in Switzerland. We tested thein vitroactivity of ceftaroline against an archived set of 60 MRSA strains from the University Hospital of Geneva collected from 1994 to 2003. Our results surprisingly revealed ceftaroline-resistant strains (MIC, >1 μg/ml in 40/60 strains; EUCAST breakpoints, susceptible [S], ≤1 μg/ml; resistant [R], >1 μg/ml) were present from 1998 to 2003. The detected resistant strains predominantly belonged to sequence type 228 (ST228) (South German clonotype) but also to ST247 (Iberian clonotype). A sequence analysis of these strains revealed missense mutations in the penicillin-binding protein 2A (PBP2A) allosteric domain (N146K or E239K and N146K-E150K-G246E). The majority of our ST228 PBP2A mutations (N146K or E150K) were distinct from ST228 PBP2A allosteric domain mutations (primarily E239K) recently described for MRSA strains collected in Thailand and Spain during the 2010 Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) global surveillance program. We also found that similar allosteric domain PBP2A mutations (N146K) correlated with ceftaroline resistance in an independent external ST228 MRSA set obtained from the nearby University Hospital of Lausanne, Lausanne, Switzerland, collected from 2003 to 2008. Thus, ceftaroline resistance was observed in our archived strains (including two examples of an MIC of 4 µg/ml for the Iberian ST247 clonotype with the triple mutation N146K/E150K/G246E), at least as far back as 1998, considerably predating the commercial introduction of ceftaroline. Our results reinforce the notion that unknown parameters can potentially exert selective pressure on PBP2A that can subsequently modulate ceftaroline resistance.

scholarly journals JNJ-Q2, a New Fluoroquinolone with PotentIn VitroActivity against Staphylococcus aureus, Including Methicillin- and Fluoroquinolone-Resistant Strains

2011 ◽  
Vol 55 (7) ◽  
pp. 3631-3634 ◽  
Author(s):  
David J. Farrell ◽  
Lisa C. Liverman ◽  
Douglas J. Biedenbach ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Broad Spectrum ◽  
The United States ◽  
Gram Positive ◽  
Content Type ◽  
Skin Structure ◽  
Resistant Strains

ABSTRACTJNJ-Q2 is a broad-spectrum bactericidal fluoroquinolone with potent activity against Gram-positive and -negative pathogens. In this study, thein vitroactivity of JNJ-Q2 was evaluated against 511 selectedStaphylococcus aureussamples isolated in 2008-2009 from patients with acute bacterial skin and skin structure infections in the United States by using reference methodology. JNJ-Q2 was the most potent fluoroquinolone tested overall (MIC50and MIC90, 0.12 and 0.5 μg/ml, respectively) and against methicillin- and fluoroquinolone-resistant subgroups in direct comparisons to moxifloxacin, levofloxacin, and ciprofloxacin (each being ≥16-fold less potent than JNJ-Q2).

scholarly journals Pharmacodynamics of Ceftaroline against Staphylococcus aureus Studied in anIn VitroPharmacokinetic Model of Infection

2013 ◽  
Vol 57 (6) ◽  
pp. 2451-2456 ◽  
Author(s):  
Alasdair P. MacGowan ◽  
Alan R. Noel ◽  
Sharon Tomaselli ◽  
Karen E. Bowker
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Exposure ◽  
Population Analysis ◽  
Intermediate Phenotype ◽  
Ceftaroline Fosamil ◽  
Content Type ◽  
Dose Ranging ◽  
Mrsa Strains ◽  
Emergence Of Resistance

ABSTRACTAnin vitrosingle-compartment dilutional pharmacokinetic model was used to study the pharmacodynamics of ceftaroline againstStaphylococcus aureus(both methicillin-susceptibleS. aureus[MSSA] and methicillin-resistantS. aureus[MRSA]). Mean serum free concentrations of ceftaroline (the active metabolite of the prodrug ceftaroline fosamil) dosed in humans at 600 mg every 12 h (q12h) were simulated, and activities against 12S. aureusstrains (3 MSSA strains and 9 MRSA strains, 3 of which had a vancomycin-intermediate phenotype) were determined. Ceftaroline produced 2.5- to 4.0-log10-unit reductions in viable counts by 24 h with all strains and a 0.5- to 4.0-log-unit drop in counts at 96 h. The antibacterial effect could not be related to the strain MIC across the ceftaroline MIC range from 0.12 to 2.0 μg/ml. In dose-ranging studies, the cumulative percentage of a 24-h period that the free drug concentration exceeded the MIC under steady-state pharmacokinetic conditions (fTMIC) of 24.5% ± 8.9% was associated with a 24-h bacteriostatic effect, one of 27.8% ± 9.5% was associated with a −1-log-unit drop, and one of 32.1% ± 8.1% was associated with a −2-log-unit drop. The MSSA and MRSA strains had similarfTMICvalues.fTMICvalues increased with increasing duration of exposure up to 96 h. Changes in ceftaroline population analysis profiles were related tofTMIC.fTMICs of <50% were associated with growth on 4× MIC recovery plates at 96 h of drug exposure. These data support the use of ceftaroline fosamil at doses of 600 mg q12h to treatS. aureusstrains with MICs of ≤2 μg/ml. AnfTMICof 25 to 30% would make a suitable pharmacodynamic index target, butfTMICvalues of ≥50% are needed to suppress the emergence of resistance and require clinical evaluation.

scholarly journals No Decrease in Susceptibility to NVC-422 in Multiple-Passage Studies with Methicillin-Resistant Staphylococcus aureus, S. aureus, Pseudomonas aeruginosa, and Escherichia coli

2012 ◽  
Vol 56 (5) ◽  
pp. 2753-2755 ◽  
Author(s):  
Louisa D'Lima ◽  
Lisa Friedman ◽  
Lu Wang ◽  
Ping Xu ◽  
Mark Anderson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Fusidic Acid ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Cross Resistance ◽  
Methicillin Resistant ◽  
Content Type ◽  
E Coli ◽  
Resistant Strains

ABSTRACTTwenty-five serial passages ofEscherichia coli,Pseudomonas aeruginosa, andStaphylococcus aureusand 50 passages of methicillin-resistantStaphylococcus aureusresulted in no significant increase in NVC-422 MICs, while ciprofloxacin MICs increased 256-fold forE. coliand 32-fold forP. aeruginosaandS. aureus. Mupirocin, fusidic acid, and retapamulin MICs for MRSA increased 64-, 256-, and 16-fold, respectively. No cross-resistance to NVC-422 was observed with mupirocin-, fusidic acid-, and retapamulin-resistant strains.

scholarly journals Comparative Activities of Telavancin Combined with Nafcillin, Imipenem, and Gentamicin against Staphylococcus aureus

2013 ◽  
Vol 57 (6) ◽  
pp. 2678-2683 ◽  
Author(s):  
Steven N. Leonard ◽  
Megan E. Supple ◽  
Ronak G. Gandhi ◽  
Meghna D. Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Utility ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Once Daily ◽  
Content Type ◽  
Resistant Strains ◽  
Synergy Test ◽  
Time Kill

ABSTRACTBeta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains ofStaphylococcus aureus, 10 methicillin-susceptibleS. aureus(MSSA), 10 methicillin-resistantS. aureus(MRSA), and 10 heterogeneously vancomycin-intermediateS. aureus(hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in anin vitropharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P≤ 0.002) and were similar to each other (P≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin againstS. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.

scholarly journals Characterization of the Retrocyclin Analogue RC-101 as a Preventative of Staphylococcus aureus Nasal Colonization

2011 ◽  
Vol 55 (11) ◽  
pp. 5338-5346 ◽  
Author(s):  
Ryan P. Lamers ◽  
Colleen R. Eade ◽  
Alan J. Waring ◽  
Amy L. Cole ◽  
Alexander M. Cole
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Treatment Options ◽  
Nasal Colonization ◽  
Proinflammatory Response ◽  
Content Type ◽  
Bactericidal Effects ◽  
Prevention Of Nosocomial Infection

ABSTRACTNasal colonization ofStaphylococcus aureusis a risk factor for pathogenic autoinfection, particularly in postoperative patients and the immunocompromised. As such, standardized preoperative nasal decolonization ofS. aureushas become a major consideration for the prevention of nosocomial infection. However, only a few treatment options for nasal decolonization are currently available, with resistance to these approaches already a concern. Here we have identified the macrocyclic θ-defensin analogue RC-101 as a promising anti-S. aureusagent for nasal decolonization. RC-101 exhibits bactericidal effects againstS. aureuswith the use ofin vitroepithelium-free systems, while also preventing the pathogen's proliferation and attachment in anex vivohuman nasal epithelial cell adhesion model and an organotypic model of human airway epithelia. Peptide concentrations as low as 2.5 μM elicited significant reductions inS. aureusgrowth in epithelium-free systems, with 10 μM concentrations being completely bactericidal for all strains tested, including USA300. Inex vivonasal colonization models, RC-101 significantly reduced adherence, survival, and proliferation ofS. aureuson human nasal epithelia. Reductions inS. aureusviability were evident in these assays, with as little as 1 μg of peptide per tissue, while 10 μg of RC-101 completely prevented adhesion of all strains tested. Furthermore, RC-101 did not exhibit cellular toxicity to human nasal epithelia at concentrations up to 200 μM, nor did it induce a proinflammatory response in these cells. Collectively, the findings of this study identify RC-101 as a potential preventative ofS. aureusnasal colonization.

scholarly journals In Vitro Evaluation of Povidone-Iodine and Chlorhexidine against Outbreak and Nonoutbreak Strains of Mycobacterium abscessus Using Standard Quantitative Suspension and Carrier Testing

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Aristine Cheng ◽  
Hsin-Yun Sun ◽  
Yi-Tzu Tsai ◽  
Un-In Wu ◽  
Yu-Chung Chuang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Best Practice ◽  
Povidone Iodine ◽  
Mycobacterium Abscessus ◽  
First Line ◽  
Outbreak Strain ◽  
Content Type ◽  
Skin Antisepsis ◽  
The Mean

ABSTRACTPovidone-iodine (PI) and chlorhexidine (CHX) are widely used antiseptics active against conventionalStaphylococcus aureus,Enterobacteriaceae,Candidaspecies, and viruses, but their efficacy againstMycobacterium abscessusremains unproven. We determined thein vitropotency of alcoholic PI and CHX againstM. abscessussubsp.abscessus(ATCC 19977),M. abscessussubsp.bolletii(BCRC 16915), and our outbreak strain ofM. abscessussubsp.massiliense(TPE 101) in reference toStaphylococcus aureus(ATCC 29213) by standard quantitative suspension and carrier methods (EN 14563). By suspension, all mycobacterial strains compared toS. aureuswere significantly more resistant to CHX, but not PI. By carrier, the mean logarithmic reductions (LR) achieved by PI under clean (dirty) conditions were 6.575 (2.482), 5.540 (2.298), 4.595 (1.967), and 1.173 (0.889), while those achieved by CHX under clean (dirty) conditions were 3.164 (5.445), 5.307 (2.564), 3.844 (2.232), and 0.863 (0.389) forS. aureus,M. abscessussubsp.bolletii,M. abscessussubsp.abscessus, andM. abscessussubsp.massiliense, respectively.M. abscessussubsp.massiliense(outbreak strain) was significantly more resistant than the other tested strains to PI and CHX. By both methods, the mean LR achieved by PI was higher than for CHX for all mycobacterial strains, but under dirty conditions, neither antiseptic was effectively mycobactericidal (LR < 5). These preliminary findings caution against the universal replacement of PI with CHX as the first-line skin antiseptic, since allM. abscessusisolates were resistant to CHX. More studies are needed to establish the best practice for skin antisepsis if mycobacterial infections are also to be prevented.

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